scholarly journals UPF1-Mediated RNA Decay—Danse Macabre in a Cloud

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 999 ◽  
Author(s):  
Daria Lavysh ◽  
Gabriele Neu-Yilik
Keyword(s):  
High Variability ◽  
Effector Proteins ◽  
Degradation Efficiency ◽  
Rna Decay ◽  
User Needs ◽  
Effector Protein ◽  
Higher Eukaryotes ◽  
Flexible Infrastructure ◽  
Nonsense Mediated Rna Decay ◽  
Central Effector

Nonsense-mediated RNA decay (NMD) is the prototype example of a whole family of RNA decay pathways that unfold around a common central effector protein called UPF1. While NMD in yeast appears to be a linear pathway, NMD in higher eukaryotes is a multifaceted phenomenon with high variability with respect to substrate RNAs, degradation efficiency, effector proteins and decay-triggering RNA features. Despite increasing knowledge of the mechanistic details, it seems ever more difficult to define NMD and to clearly distinguish it from a growing list of other UPF1-mediated RNA decay pathways (UMDs). With a focus on mammalian NMD, we here critically examine the prevailing NMD models and the gaps and inconsistencies in these models. By exploring the minimal requirements for NMD and other UMDs, we try to elucidate whether they are separate and definable pathways, or rather variations of the same phenomenon. Finally, we suggest that the operating principle of the UPF1-mediated decay family could be considered similar to that of a computing cloud providing a flexible infrastructure with rapid elasticity and dynamic access according to specific user needs.

scholarly journals The Epichloë festucae Antifungal Protein Efe-AfpA Is Also a Possible Effector Protein Required for the Interaction of the Fungus with its Host Grass Festuca rubra subsp. rubra

2021 ◽  
Vol 9 (1) ◽  
pp. 140
Author(s):  
Ruying Wang ◽  
Simin Luo ◽  
Bruce B. Clarke ◽  
Faith C. Belanger
Keyword(s):  
Disease Resistance ◽  
Insect Resistance ◽  
Effector Proteins ◽  
Antifungal Protein ◽  
Grass Species ◽  
Effector Protein ◽  
Festuca Rubra ◽  
Symbiotic Interaction ◽  
Red Fescue ◽  
Epichloë Festucae

Strong creeping red fescue (Festuca rubra subsp. rubra) is a commercially important low-maintenance turfgrass and is often naturally infected with the fungal endophyte Epichloë festucae. Epichloë spp. are endophytes of several cool-season grass species, often conferring insect resistance to the grass hosts due to the production of toxic alkaloids. In addition to insect resistance, a unique feature of the strong creeping red fescue/E. festucae symbiosis is the endophyte-mediated disease resistance to the fungal pathogen Clarireedia jacksonii, the causal agent of dollar spot disease. Such disease resistance is not a general feature of other grass/ Epichloë interactions. E. festucae isolates infecting red fescue have an antifungal protein gene Efe-afpA, whereas most other Epichloë spp. do not have a similar gene. The uniqueness of this gene suggests it may, therefore, be a component of the unique disease resistance seen in endophyte-infected red fescue. Here, we report the generation of CRISPR-Cas9 Efe-afpA gene knockouts with the goal of determining if absence of the protein in endophyte-infected Festuca rubra leads to disease susceptibility. However, it was not possible to infect plants with the knockout isolates, although infection was possible with the wild type E. festucae and with complemented isolates. This raises the interesting possibility that, in addition to having antifungal activity, the protein is required for the symbiotic interaction. The antifungal protein is a small secreted protein with high expression in planta relative to its expression in culture, all characteristics consistent with effector proteins. If Efe-AfpA is an effector protein it must be specific to certain interactions, since most Epichloë spp. do not have such a gene in their genomes.

scholarly journals Inhibition of Nonsense-Mediated RNA Decay by the Tumor Microenvironment Promotes Tumorigenesis

2011 ◽  
Vol 31 (17) ◽  
pp. 3670-3680 ◽  
Author(s):  
D. Wang ◽  
J. Zavadil ◽  
L. Martin ◽  
F. Parisi ◽  
E. Friedman ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Rna Decay ◽  
Nonsense Mediated Rna Decay

scholarly journals Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Carrie L. Shaffer ◽  
James A. D. Good ◽  
Santosh Kumar ◽  
K. Syam Krishnan ◽  
Jennifer A. Gaddy ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Small Molecules ◽  
Bacterial Pathogens ◽  
Effector Proteins ◽  
Type Iv Secretion ◽  
Target Cells ◽  
Effector Protein ◽  
Secretion Systems ◽  
Type Iv ◽  
H Pylori

ABSTRACT Bacteria utilize complex type IV secretion systems (T4SSs) to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85) that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA) and peptidoglycan into gastric epithelial cells. In H. pylori , KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori , we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs. IMPORTANCE Many human and plant pathogens utilize complex nanomachines called type IV secretion systems (T4SSs) to transport proteins and DNA to target cells. In addition to delivery of harmful effector proteins into target cells, T4SSs can disseminate genetic determinants that confer antibiotic resistance among bacterial populations. In this study, we sought to identify compounds that disrupt T4SS-mediated processes. Using the human gastric pathogen H. pylori as a model system, we identified and characterized two small molecules that prevent transfer of an oncogenic effector protein to host cells. We discovered that these small molecules also prevented the spread of antibiotic resistance plasmids in E. coli populations and diminished the transfer of tumor-inducing DNA from the plant pathogen A. tumefaciens to target cells. Thus, these compounds are versatile molecular tools that can be used to study and disarm these important bacterial machines.

The Legionella pneumophila effector RavY contributes to a replication-permissive vacuolar environment during infection

2021 ◽  
Author(s):  
Luying Liu ◽  
Craig R. Roy
Keyword(s):  
Legionella Pneumophila ◽  
Effector Proteins ◽  
Type Iv Secretion ◽  
Host Cells ◽  
Effector Protein ◽  
Intracellular Replication ◽  
Phagocytic Cells ◽  
Host Molecules ◽  
Type Iv ◽  
Legionnaires Disease

Legionella pneumophila is the causative agent of Legionnaires’ Disease and is capable replicating inside phagocytic cells such as mammalian macrophages. The Dot/Icm type IV secretion system is a L. pneumophila virulence factor that is essential for successful intracellular replication. During infection, L. pneumophila builds a replication permissive vacuole by recruiting multiple host molecules and hijacking host cellular signaling pathways, a process mediated by the coordinated functions of multiple Dot/Icm effector proteins. RavY is a predicted Dot/Icm effector protein found to be important for optimal L. pneumophila replication inside host cells. Here, we demonstrate that RavY is a Dot/Icm-translocated effector protein that is dispensable for axenic replication of L. pneumophila , but critical for optimal intracellular replication of the bacteria. RavY is not required for avoidance of endosomal maturation, nor does RavY contribute to the recruitment of host molecules found on replication-permissive vacuoles, such as ubiquitin, RAB1a, and RTN4. Vacuoles containing L. pneumophila ravY mutants promote intracellular survival but limit replication. The replication defect of the L. pneumophila ravY mutant was complemented when the mutant was in the same vacuole as wild type L. pneumophila . Thus, RavY is an effector that is essential for promoting intracellular replication of L. pneumophila once the specialized vacuole has been established.

scholarly journals Nonsense-Mediated RNA Decay Factor UPF1 Is Critical for Posttranscriptional and Translational Gene Regulation in Arabidopsis

2020 ◽  
Vol 32 (9) ◽  
pp. 2725-2741 ◽  
Author(s):  
Vivek K. Raxwal ◽  
Craig G. Simpson ◽  
Jiradet Gloggnitzer ◽  
Juan Carlos Entinze ◽  
Wenbin Guo ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Rna Decay ◽  
Decay Factor ◽  
Nonsense Mediated Rna Decay

scholarly journals Type IV Effector Proteins Involved in the Medicago-Sinorhizobium Symbiosis

2017 ◽  
Vol 30 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Matthew S. Nelson ◽  
Chan Lan Chun ◽  
Michael J. Sadowsky
Keyword(s):  
Transcriptional Activation ◽  
Sinorhizobium Meliloti ◽  
Effector Proteins ◽  
Nodule Formation ◽  
Effector Protein ◽  
In Planta ◽  
Type Iv ◽  
Rhizobial Species ◽  
Polymerase Chain ◽  
Plant Sequence

In this study, we investigated genetic elements of the type IV secretion system (T4SS) found in Sinorhizobium spp. and the role they play in symbiosis. Sinorhizobium meliloti and S. medicae each contain a putative T4SS similar to that used by Agrobacterium tumefaciens during pathogenesis. The Cre reporter assay for translocation system was used to validate potential effector proteins. Both S. meliloti and S. medicae contained the effector protein TfeA, which was translocated into the host plant. Sequence analysis revealed the presence of a nod box involved in transcriptional activation of symbiosis-related genes, upstream of the transcriptional regulator (virG) in the Sinorhizobium T4SS. Replicate quantitative reverse transcription-polymerase chain reaction analyses indicated that luteolin, released by roots and seeds of Medicago truncatula, upregulated transcription of tfeA and virG. Mutations in the T4SS apparatus or tfeA alone resulted in reduced numbers of nodules formed on M. truncatula genotypes. In addition, S. meliloti KH46c, which contains a deletion in the T4SS, was less competitive for nodule formation when coinoculated with an equal number of cells of the wild-type strain. To our knowledge, TfeA is the first T4SS effector protein identified in Sinorhizobium spp. Our results indicate that Sinorhizobium i) uses a T4SS during initiation of symbiosis with Medicago spp., and ii) alters Medicago cells in planta during symbiosis. This study also offers additional bioinformatic evidence that several different rhizobial species may use the T4SS in symbiosis with other legumes.

Distribution of espI among clinical enterohaemorrhagic and enteropathogenic Escherichia coli isolates

2004 ◽  
Vol 53 (11) ◽  
pp. 1145-1149 ◽  
Author(s):  
Rosanna Mundy ◽  
Claire Jenkins ◽  
Jun Yu ◽  
Henry Smith ◽  
Gad Frankel
Keyword(s):  
Escherichia Coli ◽  
Type Iii Secretion ◽  
Severe Disease ◽  
Pathogenicity Island ◽  
Effector Proteins ◽  
Effector Protein ◽  
Enteropathogenic Escherichia Coli ◽  
Type Iii Effector ◽  
Type Iii

Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli are important diarrhoeagenic pathogens; infection is dependent on translocation of a number of type III effector proteins. Until recently all the known effectors were encoded on the LEE pathogenicity island, which also encodes the adhesin intimin and the type III secretion apparatus. Recently, a novel non-LEE effector protein, EspI/NleA, which is required for full virulence in vivo and is encoded on a prophage, was identified. The aim of this study was to determine the distribution of espI among clinical EHEC and EPEC isolates. espI was detected in 86 % and 53 % of LEE+ EHEC and EPEC strains, respectively. Moreover, the espI gene was more commonly found in patients suffering from a more severe disease.

scholarly journals The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay

Cell ◽  
2016 ◽  
Vol 165 (2) ◽  
pp. 382-395 ◽  
Author(s):  
Eleen Y. Shum ◽  
Samantha H. Jones ◽  
Ada Shao ◽  
Jennifer Dumdie ◽  
Matthew D. Krause ◽  
...  
Keyword(s):  
Rna Decay ◽  
Nonsense Mediated Rna Decay
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